4.6 Article

The synthetic CB1 cannabinoid receptor selective agonists: Putative medical uses and their legalization

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pnpbp.2021.110301

Keywords

Anandamide; Cannabinoids; Cannabinoids-based medicines; Ligands; Sleep

Funding

  1. University of California Institute for Mexico and the United States (UC MEXUS)
  2. Consejo Nacional de Ciencia y Tecnologia (CONACyT
  3. Mexico) [CN-17-19]
  4. Escuela de Medicina, Universidad Anahuac Mayab (Merida, Yucatan. Mexico) [PresInvEMR2018]

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Δ9-THC, the major component of Cannabis sativa, exerts biological effects through activation of cannabinoid receptors CB1 and CB2. Synthetic CB1 cannabinoid receptor selective agonists show potential in therapeutic approaches, but concerns regarding side effects still exist despite positive results in experimental models and preclinical trials.
More than 500 molecules have been identified as components of Cannabis sativa (C. sativa), of which the most studied is A9-tetrahydrocannabinol (A9-THC). Several studies have suggested that A9-THC exerts diverse biological effects, ranging from fragmentation of DNA to behavioral disruptions. Currently, it is accepted that most of the pharmacological properties of A9-THC engage the activation of the cannabinoid receptors, named CB1 and CB2. Interestingly, multiple pieces of evidence have suggested that the cannabinoid receptors play an active role in the modulation of several diseases leading to the design of synthetic cannabinoid-like compounds. Advances in the development of synthetic CB1 cannabinoid receptor selective agonists as therapeutical approaches are, however, limited. This review focuses on available evidence searched in PubMed regarding the synthetic CB1 cannabinoid receptor selective agonists such as AM-1235, arachidonyl-2 ' chloroethylamide (ACEA), CP 50,556-1 (Levonantradol), CP-55,940, HU-210, JWH-007, JWH-018, JWH-200 (WIN 55,225), methanandamide, nabilone, O-1812, UR-144, WIN 55,212-2, nabiximols, and dronabinol. Indeed, it would be ambitious to describe all available evidence related to the synthetic CB1 cannabinoid receptor selective agonists. However, and despite the positive evidence on the positive results of using these compounds in experimental models of health disturbances and preclinical trials, we discuss evidence in regards some concerns due to side effects.

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